US4179565A - 2,5-Dimethyl-benzo[b]-thieno[2,3-f]morphan and precursors thereof - Google Patents

2,5-Dimethyl-benzo[b]-thieno[2,3-f]morphan and precursors thereof Download PDF

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Publication number
US4179565A
US4179565A US05/871,653 US87165378A US4179565A US 4179565 A US4179565 A US 4179565A US 87165378 A US87165378 A US 87165378A US 4179565 A US4179565 A US 4179565A
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US
United States
Prior art keywords
benzo
dimethyl
thienylmethyl
tetrahydropyridine
morphan
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Expired - Lifetime
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US05/871,653
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English (en)
Inventor
Ricardo Granados Jarque
Mercedes Alvarez Domingo
Juan Bosch Cartes
Cristobal Martinez Roldan
Fernando Rabadan Peinado
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Laboratorios Made SA
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Laboratorios Made SA
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/08—Bridged systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids

Definitions

  • the present invention relates to the preparation of 2,5-dimethyl-benzo[b]thieno[2,3-f]morphan (I) to the preparation of two of its intermediates, 2-(3-benzo[b]thienylmethyl)-1,4-dimethyl-1,2,3,6-tetrahydropyridine (II) and 2-(3-benzo[b]thienylmethyl)-1,4-dimethyl-1,2,5,6-tetrahydropyridine (III) and the addition salts thereof with pharmacologically acceptable acids.
  • the organic layer gives a mixture from which 2-(3-benzo[b]-thienylmethyl)-1,4-dimethyl-1,2,3,6-tetrahydropyridine (II) and 2-(3-benzo[b]-thienylmethyl)-1,4-dimethyl-1,2,5,6-tetrahydropyridine (III) are separated by distillation and subsequent fractional crystallisation of the corresponding picrates.
  • the previously obtained raw mixture is heated to 135° C. for 12 h. in the presence of a strong acid, for example 48% aqueous hydrobromic acid. It is poured over ice and water, rendered alkaline with ammonium hydroxide and extracted with ether, yielding 2,5-dimethyl-benzo[b]thieno[2,3-f]-morphan (I).
  • a strong acid for example 48% aqueous hydrobromic acid. It is poured over ice and water, rendered alkaline with ammonium hydroxide and extracted with ether, yielding 2,5-dimethyl-benzo[b]thieno[2,3-f]-morphan (I).
  • the column of the reactor is packed with 70 gr. of magnesium in chips, alternating with thin layers of mercuric chloride, and is covered with a saturated solution of mercuric chloride in anhydrous ether. It is left standing for 48 h., 250 ml. of anhydrous ether then being placed in the flask and refluxed for 2 h.
  • the flask is replaced by another provided with mechanical stirring, in which 19 gr. of 1,4-dimethylpyridinium iodide in suspension with 300 ml.
  • the thermal analgesic effect was studied on I.C.R. Swiss albino mice.
  • the hot plate technique was used at 55° C. Batches of 10 mice were made.
  • mice were administered intraperitoneally and after 30 minutes the mice were placed on the hot plate, counting the number of seconds they took to jump. Batches of control animals which are only injected with distilled water are used.
  • Product I has analgesic activity which is not significantly different from that of dextropropoxyphene.
  • Product II is lacking thermal analgesic activity.
  • Product III is lacking thermal analgesic activity.
  • mice The analgesic effect was studied on I.C.R. Swiss albino mice with the acetic acid writhing technique. Batches of 10 mice were made.
  • the products under study were administered intraperitoneally and after 30 minutes 0.25 ml of 1% acetic acid are injected intraperitoneally.
  • a batch of control animals which only receive acetic acid is used.
  • the number of writhes in each mouse is counted 20 minutes after administration of the acetic acid.
  • Product I has greater analgesic activity then dextropropoxyphene.
  • the analgesic activity of product II is not significantly different from that of dextropropoxyphene.
  • the analgesic activity of product III is not significantly different from that of dextropropoxyphene.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pain & Pain Management (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Plural Heterocyclic Compounds (AREA)
US05/871,653 1977-02-25 1978-01-23 2,5-Dimethyl-benzo[b]-thieno[2,3-f]morphan and precursors thereof Expired - Lifetime US4179565A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ES456283A ES456283A1 (es) 1977-02-25 1977-02-25 Un procedimiento para la obetencion de 2,5-dimetil-benzo (b)tieno (2,3-f) morfano.
ES456.283 1977-02-25

Publications (1)

Publication Number Publication Date
US4179565A true US4179565A (en) 1979-12-18

Family

ID=8473232

Family Applications (1)

Application Number Title Priority Date Filing Date
US05/871,653 Expired - Lifetime US4179565A (en) 1977-02-25 1978-01-23 2,5-Dimethyl-benzo[b]-thieno[2,3-f]morphan and precursors thereof

Country Status (11)

Country Link
US (1) US4179565A (de)
JP (1) JPS53137999A (de)
AR (1) AR213560A1 (de)
AT (1) AT357273B (de)
BE (1) BE863266A (de)
DE (1) DE2807077C3 (de)
ES (1) ES456283A1 (de)
FR (1) FR2381772A1 (de)
GB (1) GB1574257A (de)
NL (1) NL7801992A (de)
PT (1) PT67701B (de)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4281130A (en) * 1979-05-24 1981-07-28 Sterling Drug Inc. Lower-alkyl 4,6,7,8,8a-9-hexahydro-6,9-ethanothieno[3,2-f]indolizine-10-carboxylate
US4496572A (en) * 1981-08-26 1985-01-29 Pfizer Inc. Benzo-fused thromboxane synthetase inhibitors

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3382249A (en) * 1964-10-20 1968-05-07 Sterling Drug Inc 1, 2, 3, 4, 5, 6-hexahydro-3-(cycloalkyl-lower alkylene-)-2, 6-methano-3-naphth [2, 1-f]azocines

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3382249A (en) * 1964-10-20 1968-05-07 Sterling Drug Inc 1, 2, 3, 4, 5, 6-hexahydro-3-(cycloalkyl-lower alkylene-)-2, 6-methano-3-naphth [2, 1-f]azocines

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Montzka, T., et al., J. Het. Chem., 11, 853-855, (1974). *
Perry, R., et al., J. Med. Chem., 10, 1184-1186, (1967). *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4281130A (en) * 1979-05-24 1981-07-28 Sterling Drug Inc. Lower-alkyl 4,6,7,8,8a-9-hexahydro-6,9-ethanothieno[3,2-f]indolizine-10-carboxylate
US4496572A (en) * 1981-08-26 1985-01-29 Pfizer Inc. Benzo-fused thromboxane synthetase inhibitors
US4590200A (en) * 1981-08-26 1986-05-20 Pfizer Inc. Naphthalene thromboxane synthetase inhibitors

Also Published As

Publication number Publication date
DE2807077B2 (de) 1979-10-31
BE863266A (fr) 1978-05-16
ES456283A1 (es) 1978-04-01
AT357273B (de) 1980-06-25
NL7801992A (nl) 1978-08-29
ATA118678A (de) 1979-11-15
PT67701A (en) 1978-03-01
GB1574257A (en) 1980-09-03
DE2807077A1 (de) 1978-08-31
JPS53137999A (en) 1978-12-01
AR213560A1 (es) 1979-02-15
FR2381772A1 (fr) 1978-09-22
DE2807077C3 (de) 1980-07-10
PT67701B (en) 1980-05-05

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